Header

UZH-Logo

Maintenance Infos

The T cell repertoire in tumors overlaps with pulmonary inflammatory lesions in patients treated with checkpoint inhibitors


Läubli, Heinz; Koelzer, Viktor H; Matter, Matthias S; Herzig, Petra; Dolder Schlienger, Béatrice; Wiese, Mark Nikolaj; Lardinois, Didier; Mertz, Kirsten D; Zippelius, Alfred (2018). The T cell repertoire in tumors overlaps with pulmonary inflammatory lesions in patients treated with checkpoint inhibitors. OncoImmunology, 7(2):e1386362.

Abstract

Cancer immunotherapy with antibodies targeting immune checkpoints such as the PD-1/PD-L1 pathway have emerged as breakthrough treatment for multiple solid tumors with high response rates and durable remissions. Despite the benefit for patients and encouraging safety profile, severe inflammatory reactions are observed in some patients. Such immune-related adverse events (irAEs) frequently lead to temporary or permanent cessation of the treatment and require systemic immunosuppression yet underlying mechanisms of irAEs are not known in detail. Here, we describe the T cell-mediated immune reaction in irAE lesions of four patients that developed pneumonitis during therapy with a PD-1 blocking antibody. Immunohistochemical analysis was performed to map the environment of the inflammatory lesions. Tumor infiltrating T cell clones were identified by sequencing the T cell receptor, and comparison with clones from peripheral blood or secondary lymphoid organs. A significant overlap of clones infiltrating irAE lesions and tumors was found. The most prevalent clones were also expanded in peripheral blood, but only a minor fraction of clonal overlap was found. Our findings suggest that irAE lesions in patients under PD-1 blockade are infiltrated by T cells with similar specificity as tumor-infiltrating T cells. These results raise the possibility that the immune response is elicited in these patients against antigens shared by the tumor and distant organs affected by irAEs.

Abstract

Cancer immunotherapy with antibodies targeting immune checkpoints such as the PD-1/PD-L1 pathway have emerged as breakthrough treatment for multiple solid tumors with high response rates and durable remissions. Despite the benefit for patients and encouraging safety profile, severe inflammatory reactions are observed in some patients. Such immune-related adverse events (irAEs) frequently lead to temporary or permanent cessation of the treatment and require systemic immunosuppression yet underlying mechanisms of irAEs are not known in detail. Here, we describe the T cell-mediated immune reaction in irAE lesions of four patients that developed pneumonitis during therapy with a PD-1 blocking antibody. Immunohistochemical analysis was performed to map the environment of the inflammatory lesions. Tumor infiltrating T cell clones were identified by sequencing the T cell receptor, and comparison with clones from peripheral blood or secondary lymphoid organs. A significant overlap of clones infiltrating irAE lesions and tumors was found. The most prevalent clones were also expanded in peripheral blood, but only a minor fraction of clonal overlap was found. Our findings suggest that irAE lesions in patients under PD-1 blockade are infiltrated by T cells with similar specificity as tumor-infiltrating T cells. These results raise the possibility that the immune response is elicited in these patients against antigens shared by the tumor and distant organs affected by irAEs.

Statistics

Citations

Dimensions.ai Metrics
33 citations in Web of Science®
35 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

20 downloads since deposited on 26 Sep 2019
9 downloads since 12 months
Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Pathology and Molecular Pathology
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Health Sciences > Immunology and Allergy
Life Sciences > Immunology
Health Sciences > Oncology
Language:English
Date:2018
Deposited On:26 Sep 2019 13:47
Last Modified:29 Jul 2020 11:21
Publisher:Taylor & Francis
ISSN:2162-4011
OA Status:Hybrid
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.1080/2162402X.2017.1386362
PubMed ID:29308309

Download

Hybrid Open Access

Download PDF  'The T cell repertoire in tumors overlaps with pulmonary inflammatory lesions in patients treated with checkpoint inhibitors'.
Preview
Content: Published Version
Filetype: PDF
Size: 810kB
View at publisher